Questionable Hope for CCSVI in Multiple Sclerosis
May 12, 2011
Once again, multiple sclerosis patients’ area buzz over a new theory and treatment for the disease. The theory is called chronic cerebrospinal venous insufficiency (CCSVI); and, this time, social media is driving the patient excitement.
CCSVI is based on a controversial idea that impaired venous drainage of the brain due to blockage in venous structures causes MS. Increase in venous pressure promotes leakage of blood across capillaries, with inflammation resulting from the iron deposition into the brain. In 2009 Paolo Zamboni, M.D., reported that virtually all MS patients in a study had abnormalities in the jugular or azygous veins, whereas no control patients had such findings. The Zamboni, or Liberation, procedure involves either angioplasty or stenting of the abnormal vein. Many MS patients are understandably enthusiastic about this theory and treatment.
There are, however, a number of problems with the CCSVI theory that patients and MS neurologists should consider.
- Diagnostic criteria for CCSVI are not standardized or accepted
- CCSVI does not seem to explain the distribution of white matter lesions or the relapsing and remitting course that most patients experience
- CCSVI does not explain the presence of inflammation in MS lesions
- Iron in MS lesions is contained within macrophages, not erythrocytes or free, as predicted by the CCSVI theory
- Other diseases with increased venous pressure do not resemble MS
- Venous drainage is highly redundant, so stricture of a vein usually does not increase venous pressure in the brain
- Changes in muscle tone or posture from neurological disease may explain some venous blockages; and neurological disease can lead to lower venous blood flow due to circulatory auto regulation
Studies that have been performed to date have not supported the CCSVI theory. Preliminary results from the Buffalo Neuroimaging Analysis Center at the University at Buffalo, The State University of New York, found 56 percent of patients with MS, 42 percent of those with neurological diseases other than MS, and 23 percent of controls met criteria for CCSVI. This group found a decrease in cerebral venous volume in MS patients compared to normal, whereas blockage in venous flow would be expected to induce vascular dilation and increased venous volume.
At the recent ECTRIMS (European Committee for the Treatment and Research of Multiple Sclerosis) meeting in Sweden, groups from Gotteborg, Berlin, Padua, Amsterdam and London found no evidence for venous obstruction in MS patients compared to controls. A study from London, Ontario, found that venous blockage increased with age in both MS and controls. A study from Beirut, Lebanon, found venous changes in only 9 percent of patients after their first MS attack, increasing to 92 percent with advanced MS, possibly suggesting a late finding that is unrelated to the cause of the disease. Nevertheless, as anecdotal reports continue to circulate of individual patients with dramatic responses to treatment of CCSVI, the theory has been of great interest among MS patients and has become the subject of a significant number of studies.
Before CCSVI can be considered as contributing to MS, three criteria should be required.
- Venous blockage must be shown to be increased in MS patients relative to healthy controls and other neurological diseases. This would demonstrate an association between CCSVI and MS, but not prove causation.
- Treatment of CCSVI should stop the progression of MS symptoms in placebo controlled, blinded, multi-center studies. This would prove that CCSVI contributes to MS, but not prove causation.
- MS should develop in humans or animals with venous blockage.
The scientific community is taking CCSVI very seriously. Most of the studies currently under way are testing whether MS patients have venous blockage. The National MS Society and the MS Society of Canada funded seven 24-month studies in June 2010, totaling $2,400,000 of ultrasound, MRI and angiographic techniques to determine whether venous blockage is specific to MS patients in both adult and pediatric populations. The MS Society of Italy is contributing £900,000 (nearly $1.3 million) to study the question. The Buffalo Neuroimaging Analysis Center is conducting a study of venous imaging, as well as a small treatment trial. Saskatchewan and MS Research Australia have also initiated large studies.
The risks of the Liberation procedure in MS are not entirely understood, though stent migration and fatal intracerebral bleeding have already been described. Only controlled studies will teach us the true complication rate. In the meantime, most MS neurologists are recommending that patients await the results of current studies before proceeding with this controversial treatment.